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Knowledge on biodiversity has been acquired parallel to the modification of the environment so that the sites on which more information is available are those which have simultaneously had more anthropogenic disturbances. Isla de los Estados, a Reserve in Tierra del Fuego Province, has suffered few changes due to the difficulties in reaching it and the hostility of its environment. However the possibilities to actualise its tourist potential are ever closer as the demand for pristine places increases and the authorities have before them an uncommon opportunity to sanction a Management Plan for the area before the area is used. The first step in the preparation of such a Management Plan is knowledge of the area and with this end in view it was decided to draw the vegetation map for the island. The map was done using ETM+ Landsat 7 images, aerial photographs and superimposing data from the SRTM sensor. The areas were classified and the species distribution described according to the information of different authors. Isla de los Estados has ten different environments, a low proportion of endemic species in relation to other oceanic islands and a very low proportion of exotic species. The data produced must be verified in the field to allow the delimitation of areas of use and the planning of actions according to conservation criteria. [ABSTRACT FROM AUTHOR]

Over the past decade, scholars have explored whether the stigma associated with sexual violence (SV) represents a risk factor for psychopathology and related comorbidities following SV. We conducted a scoping review to summarize and evaluate the state of this burgeoning literature. We included studies from Pubmed, APA PsychInfo, Embase, CINAHL Plus, Social Science Premium, and Web of Science that quantified stigma related to SV. Studies were screened and abstracted in accordance with the PRISMA-SCR guidelines for scoping reviews. Our final sample contained 62 studies. We address two key questions about SV stigma. First, is SV a stigmatized status? Articles ( n  = 14) provided evidence for SV stigma among potential stigmatizers (e.g., individuals who may perpetuate stigma) across a range of methods (e.g., vignettes) and outcomes (e.g., desire for social distance). Additional work ( n  = 20) corroborates perceptions of SV stigma among targets (i.e., SV survivors). Second, what are the psychosocial consequences of SV stigma? We reviewed studies ( n  = 28) demonstrating that SV stigma is correlated with a range of adverse psychosocial outcomes-including anxiety, depression, posttraumatic stress disorder, problematic drinking, and somatic symptoms-among individuals experiencing multiple types of SV (e.g., childhood sexual abuse and sexual assault). Thus, emerging evidence suggests that SV stigma may be a critical determinant of risk and recovery following SV exposure. However, a number of limitations were observed, including that SV stigma has not been consistently measured and that the literature has not fully incorporated stigma constructs, such as concealment and structural stigma. We offer several recommendations to advance this line of work., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Low-income countries bear a growing and disproportionate burden of oral diseases. With the World Health Organization targeting universal oral health coverage by 2030, assessing the state of oral health coverage in these resource-limited nations becomes crucial. This research seeks to examine the political and resource commitments to oral health, along with the utilization rate of oral health services, across 27 low-income countries., Methods: We investigated five aspects of oral health coverage in low-income countries, including the integration of oral health in national health policies, covered oral health services, utilization rates, expenditures, and the number of oral health professionals. A comprehensive search was conducted across seven bibliographic databases, three grey literature databases, and national governments' and international organizations' websites up to May 2023, with no linguistic restrictions. Countries were categorized into "full integration", "partial integration", or "no integration" based on the presence of dedicated oral health policies and the frequency of oral health mentions. Covered oral health services, utilization rates, expenditure trends, and the density of oral health professionals were analyzed using evidence from reviews and data from World Health Organization databases., Results: A total of 4242 peer-reviewed and 3345 grey literature texts were screened, yielding 12 and 84 files respectively to be included in the final review. Nine countries belong to "full integration" and thirteen countries belong to "partial integration", while five countries belong to "no integration". Twelve countries collectively covered 26 types of oral health care services, with tooth extraction being the most prevalent service. Preventive and public health-based oral health interventions were scarce. Utilization rates remained low, with the primary motivation for seeking care being dental pain relief. Expenditures on oral health were minimal, predominantly relying on domestic private sources. On average, the 27 low-income countries had 0.51 dentists per 10,000 population, contrasting with 2.83 and 7.62 in middle-income and high-income countries., Conclusions: Oral health care received little political and resource commitment toward achieving universal health coverage in low-income countries. Urgent action is needed to mobilize financial and human resources, and integrate preventive and public health-based interventions., (© 2024. The Author(s).)

Objective: This study evaluated how surgical and anesthesiology departments adapted their resources in response to the coronavirus disease 2019 (COVID-19) pandemic., Design: This scoping review used the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews protocol, with Covidence as a screening tool. An initial search of PubMed, Embase, Web of Science, Global Index Medicus, and Cochrane Systematic Reviews returned 6,131 results in October 2021. After exclusion of duplicates and abstract screening, 415 articles were included. After full-text screening, 108 articles remained., Results: Most commonly, studies were retrospective in nature (47.22 percent), with data from a single institution (60.19 percent). Nearly all studies occurred in high-income countries (HICs), 78.70 percent, with no articles from low-income countries. The reported responses to the COVID-19 pandemic involving surgical departments were grouped into seven categories, with multiple responses reported in some articles for a total of 192 responses. The most frequently reported responses were changes to surgical department staffing (29.17 percent) and task-shifting or task-sharing of personnel (25.52 percent)., Conclusion: Our review reflects the mechanisms by which hospital surgical systems responded to the initial stress of the COVID-19 pandemic and reinforced the many changes to hospital policy that occurred in the pandemic. Healthcare systems with robust surgical systems were better able to cope with the initial stress of the COVID-19 pandemic. The well-resourced health systems of HICs reported rapid and dynamic changes by providers to assist in and ultimately improve the care of patients during the pandemic. Surgical system strengthening will allow health systems to be more resilient and prepared for the next disaster.

Purpose: Testing for pathogenic variants can aid in oncologic risk stratification and identification of targeted therapies. Despite known disparities in access to prostate cancer (PCa) care, little has been written about access to germline genetic testing (GGT) for Black men and other historically marginalized populations. This systematic review sought to delineate racial/ethnic disparities in GGT for PCa., Methods: This systematic review identified articles published from January 1996 through May 2021 in PubMed, Web of Science, and Embase. We included studies that reported rates of GGT in men with PCa in the United States by race/ethnicity as reflective of routine clinical care or research. A narrative synthesis was performed., Results: Of 4,309 unique records, 91 studies examining 50 unique study populations met inclusion criteria. Of these, four populations included men who received GGT through routine clinical care, accounting for 4,415 men (72.6% White and 7.2% Black). The other 46 populations included men who received GGT as part of a research study, accounting for 30,824 men (64.3% White and 21.6% Black). Of these 46 research populations, 19 used targeted methods to increase recruitment from a specific demographic., Conclusion: Most studies that report GGT rates by race/ethnicity are in research settings. Many of these studies used targeted recruitment methods and subsequently have a greater proportion of Black men than clinical and US population-based studies. Other historically marginalized populations are not well represented. There remains a knowledge gap regarding the extent of racial disparities in the use of GGT, particularly in the clinical setting.

Several peer-reviewed papers and reviews have examined the relationship between exposure to air pollution and COVID-19 spread and severity. However, many of the existing reviews on this topic do not extensively present the statistical challenges associated with this field, do not provide comprehensive guidelines for future researchers, and review only the results of a relatively small number of papers. We reviewed 139 papers, 127 of which reported a statistically significant positive association between air pollution and adverse COVID-19 health outcomes. Here, we summarize the evidence, describe the statistical challenges, and make recommendations for future research. To summarize the 139 papers with data from geographical locations around the world, we also present anopen-source data visualization tool that summarizes these studies and allows the research community to contribute evidence as new research papers are published.

The effect of emergency department (ED) length of stay (EDLOS) on in-hospital mortality (IHM) remains unclear. The aim of this systematic review and meta-analysis was to determine the association between EDLOS and IHM. We searched the PubMed, Medline, Embase, Web of Science, Cochrane Controlled Register of Trials, CINAHL, PsycInfo, and Scopus databases from their inception until 14−15 January 2022. We included studies reporting the association between EDLOS and IHM. A total of 11,337 references were identified, and 52 studies (total of 1,718,518 ED patients) were included in the systematic review and 33 in the meta-analysis. A statistically significant association between EDLOS and IHM was observed for EDLOS over 24 h in patients admitted to an intensive care unit (ICU) (OR = 1.396, 95% confidence interval [CI]: 1.147 to 1.701; p < 0.001, I2 = 0%) and for low EDLOS in non-ICU-admitted patients (OR = 0.583, 95% CI: 0.453 to 0.745; p < 0.001, I2 = 0%). No associations were detected for the other cut-offs. Our findings suggest that there is an association between IHM low EDLOS and EDLOS exceeding 24 h and IHM. Long stays in the ED should not be allowed and special attention should be given to patients admitted after a short stay in the ED.

Background: Dialysis patients have been shown to have low serum carnitine due to poor nutrition, deprivation of endogenous synthesis from kidneys, and removal by hemodialysis. Carnitine deficiency leads to impaired cardiac function and dialysis-related hypotension which are associated with increased mortality. Supplementing with levocarnitine among hemodialysis patients may diminish incidence of intradialytic hypotension. Data on this topic, however, lacks consensus., Methods: We conducted electronic searches in PubMed, Embase and Cochrane Central Register of Controlled Trials from January 1960 to 19th November 2021 to identify randomized controlled studies (RCTs), which examined the effects of oral or intravenous levocarnitine (L-carnitine) on dialysis-related hypotension among hemodialysis patients. The secondary outcome was muscle cramps. Study results were pooled and analyzed utilizing the random-effects model. Trial sequential analysis (TSA) was performed to assess the strength of current evidence., Results: Eight trials with 224 participants were included in our meta-analysis. Compared to control group, L-carnitine reduced the incidence of dialysis-related hypotension among hemodialysis patients (pooled OR = 0.26, 95% CI [0.10-0.72], p = 0.01, I2 = 76.0%). TSA demonstrated that the evidence was sufficient to conclude the finding. Five studies with 147 participants showed a reduction in the incidence of muscle cramps with L-carnitine group (pooled OR = 0.22, 95% CI [0.06-0.81], p = 0.02, I2 = 74.7%). However, TSA suggested that further high-quality studies were required. Subgroup analysis on the route of supplementation revealed that only oral but not intravenous L-carnitine significantly reduced dialysis-related hypotension. Regarding dose and duration of L-carnitine supplementation, the dose > 4,200 mg/week and duration of at least 12 weeks appeared to prevent dialysis-related hypotension., Conclusion: Supplementing oral L-carnitine for at least three months above 4,200 mg/week helps prevent dialysis-related hypotension. L-carnitine supplementation may ameliorate muscle cramps. Further well-powered studies are required to conclude this benefit., Competing Interests: The authors have declared that no competing interests exist.

Significant gaps remain in understanding the response of plant reproduction to environmental change. This is partly because measuring reproduction in long-lived plants requires direct observation over many years and such datasets have rarely been made publicly available. Here we introduce MASTREE+, a data set that collates reproductive time-series data from across the globe and makes these data freely available to the community. MASTREE+ includes 73,828 georeferenced observations of annual reproduction (e.g. seed and fruit counts) in perennial plant populations worldwide. These observations consist of 5971 population-level time-series from 974 species in 66 countries. The mean and median time-series length is 12.4 and 10 years respectively, and the data set includes 1122 series that extend over at least two decades (≥20 years of observations). For a subset of well-studied species, MASTREE+ includes extensive replication of time-series across geographical and climatic gradients. Here we describe the open-access data set, available as a.csv file, and we introduce an associated web-based app for data exploration. MASTREE+ will provide the basis for improved understanding of the response of long-lived plant reproduction to environmental change. Additionally, MASTREE+ will enable investigation of the ecology and evolution of reproductive strategies in perennial plants, and the role of plant reproduction as a driver of ecosystem dynamics., (© 2022 The Authors. Global Change Biology published by John Wiley & Sons Ltd.)

Background: While artificial intelligence (AI) offers possibilities of advanced clinical prediction and decision-making in healthcare, models trained on relatively homogeneous datasets, and populations poorly-representative of underlying diversity, limits generalisability and risks biased AI-based decisions. Here, we describe the landscape of AI in clinical medicine to delineate population and data-source disparities., Methods: We performed a scoping review of clinical papers published in PubMed in 2019 using AI techniques. We assessed differences in dataset country source, clinical specialty, and author nationality, sex, and expertise. A manually tagged subsample of PubMed articles was used to train a model, leveraging transfer-learning techniques (building upon an existing BioBERT model) to predict eligibility for inclusion (original, human, clinical AI literature). Of all eligible articles, database country source and clinical specialty were manually labelled. A BioBERT-based model predicted first/last author expertise. Author nationality was determined using corresponding affiliated institution information using Entrez Direct. And first/last author sex was evaluated using the Gendarize.io API., Results: Our search yielded 30,576 articles, of which 7,314 (23.9%) were eligible for further analysis. Most databases came from the US (40.8%) and China (13.7%). Radiology was the most represented clinical specialty (40.4%), followed by pathology (9.1%). Authors were primarily from either China (24.0%) or the US (18.4%). First and last authors were predominately data experts (i.e., statisticians) (59.6% and 53.9% respectively) rather than clinicians. And the majority of first/last authors were male (74.1%)., Interpretation: U.S. and Chinese datasets and authors were disproportionately overrepresented in clinical AI, and almost all of the top 10 databases and author nationalities were from high income countries (HICs). AI techniques were most commonly employed for image-rich specialties, and authors were predominantly male, with non-clinical backgrounds. Development of technological infrastructure in data-poor regions, and diligence in external validation and model re-calibration prior to clinical implementation in the short-term, are crucial in ensuring clinical AI is meaningful for broader populations, and to avoid perpetuating global health inequity., Competing Interests: Leo Anthony Celi is the Editor-in Chief of PLOS Digital Health and Judy Gichoya Wawira is a Section Editor for PLOS Digital Health., (Copyright: © 2022 Celi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

There is growing support to reverse mass incarceration in the United States, especially in the wake of the COVID-19 pandemic. Little is known about what types and scale of community investments are most effective to support mass decarceration. Using a public health prevention framework, we conducted a scoping review to examine community-based programs that reduced criminal legal involvement. We searched PubMed, Embase and three EBSCO databases from 1990 through September 2019 for all experimental or quasi-experimental studies testing interventions pertaining to education, housing, healthcare, employment, or social support services and how they affected an individual's criminal legal outcomes. Our review identified 53 studies that demonstrated the efficacy of early childhood educational interventions and nurse-family partnership programs, post-secondary education for incarcerated students, navigation programs linking incarcerated people to community resources, and peer support upon release to reduce criminal legal system exposure. In concert with legislative action to end mass incarceration, additional research is needed to test interventions designed to achieve mass decarceration which cross multiple domains, interrogate community-level impacts and ascertain long-term outcomes., Competing Interests: The authors have no competing interests to disclose., (© 2021 The Authors.)

Aim: To perform a systematic review of cardiopulmonary resuscitation (CPR) and/or defibrillation in the prone position compared to turning the patient supine prior to starting CPR and/or defibrillation., Methods: The search included PubMed, Embase, Web of Science, Cochrane, CINAHL Plus, and medRxiv on December 9, 2020. The population included adults and children in any setting with cardiac arrest while in the prone position. The outcomes included arterial blood pressure and end-tidal capnography during CPR, time to start CPR and defibrillation, return of spontaneous circulation, survival and survival with favorable neurologic outcome to discharge, 30 days or longer. ROBINS-I was performed to assess risk of bias for observational studies., Results: The systematic review identified 29 case reports (32 individual cases), two prospective observational studies, and two simulation studies. The observational studies enrolled 17 patients who were declared dead in the supine position and reported higher mean systolic blood pressure from CPR in prone position (72 mmHg vs 48 mmHg, p  < 0.005; 79 ± 20 mmHg vs 55 ± 20 mmHg, p  = 0.028). One simulation study reported a faster time to defibrillation in the prone position. Return of spontaneous circulation, survival to discharge or 30 days were reported in adult and paediatric case reports. Critical risk of bias limited our ability to perform pooled analyses., Conclusions: We identified a limited number of observational studies and case reports comparing prone versus supine CPR and/or defibrillation. Prone CPR may be a reasonable option if immediate supination is difficult or poses unacceptable risks to the patient., (© 2021 The Authors. Published by Elsevier B.V.)

Background: Mobile health (mHealth) have significantly advanced evaluating neurocognitive functions; but, few reports have documented whether they validate neurocognitive impairments as well as paper-and-pencil neuropsychological tests., Objective: To meta-analyze the correlation between mobile applications for neuropsychological tests and validated paper-and-pencil neuropsychological tests for evaluating neurocognitive impairments., Method: We used PubMed, Embase, Cochrane, Web of Science, and IEEE Explorer through January 2020 to identify studies that compared mobile applications for neuropsychological tests vs. paper-and-pencil neurophysiological tests. We used random-effects models via the DerSimonian and Laird method to extract pooled Pearson's correlation coefficients and we stratified by study design., Result: Nine out of 4639 screened articles (one RCT and eight prospective longitudinal case series) were included. For the observational studies, there was a statistically significant strong and direct correlation between mobile applications for neuropsychological test scores and validated paper-and-pencil neuropsychological assessment scores (r = 0.70; 95% CI 0.59, 0.79; I 2  = 74.5%; p- heterogeneity <0.001). Stronger results were seen for the RCT (r = 0.92; 95% CI 0.77, 0.97)., Conclusion: This meta-analysis showed a statistically significant correlation between mobile applications and the validated paper-and-pencil neuropsychological assessments analyzed for the evaluation of neurocognitive impairments., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Purpose: Prostate cancer is most commonly an indolent disease, especially when detected at a localized stage. Unlike other tumors that may benefit from timely receipt of definitive therapy, it is generally accepted that treatment delays for localized prostate cancer are acceptable, especially for low risk prostate cancer. Since treatment delay for intermediate risk and high risk disease is more controversial, we sought to determine if delays for these disease states negatively impacted oncological outcomes., Materials and Methods: We conducted a systematic review of the literature with searches of Medline, EMBASE and the Cochrane Database of Systematic Reviews from inception to June 30, 2020. General study characteristics as well as study population and delay information were collected. The outcomes of interest extracted included biochemical recurrence, pathological features (positive surgical margins, upgrading, extracapsular extension, and other pathological features), cancer specific survival and overall survival., Results: After identifying 1,793 unique references, 24 manuscripts met criteria for data extraction, 15 of which were published after 2013. Based on our review, delays up to 3 months are safe for all localized prostate cancer and are not associated with worse oncological outcomes. Some studies identified worse oncological outcomes as a result of delays beyond 6 to 9 months. However, these studies are counterbalanced by others finding no statistically significant association with delays up to 12 months. Studies that did find worse outcomes as a result of delays identified a higher risk of biochemical recurrence and worse pathological outcomes but not worse cancer specific or overall survival., Conclusions: Definitive treatment for intermediate risk and high risk prostate cancer can be delayed up to 3 months without any oncological consequences. Some evidence suggests that there is a higher risk of biochemical recurrence and worse pathological outcomes associated with delays beyond 6 to 9 months. To date, there are no reports of worse cancer specific survival or overall survival as a result of delayed treatment for intermediate risk and high risk prostate cancer.

Objective: This review seeks to establish the incidence of adverse outcomes associated with minimally invasive tissue extraction at the time of surgical procedures for myomas., Data Sources: Articles published in the following databases without date restrictions: PubMed, EMBASE, Web of Science, Cochrane Database of Systematic Reviews and Trials. Search was conducted on March 25, 2020., Methods of Study Selection: Included studies evaluated minimally invasive surgical procedures for uterine myomas involving morcellation. This review did not consider studies of nonuterine tissue morcellation, studies involving uterine procedures other than hysterectomy or myomectomy, studies involving morcellation of known malignancies, nor studies concerning hysteroscopic myomectomy. A total of 695 studies were reviewed, with 185 studies included for analysis., Tabulation, Integration, and Results: The following variables were extracted: patient demographics, study type, morcellation technique, and adverse outcome category. Adverse outcomes included prolonged operative time, morcellation time, blood loss, direct injury from a morcellator, dissemination of tissue (benign or malignant), and disruption of the pathologic specimen., Conclusion: Complications related to morcellation are rare; however, there is a great need for higher quality studies to evaluate associated adverse outcomes., (Copyright © 2020 AAGL. Published by Elsevier Inc. All rights reserved.)

Objective: The objective of this study was to evaluate the effect of skipping breakfast on body composition and cardiometabolic risk factors., Methods: This study conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) evaluating breakfast skipping compared with breakfast consumption. Inclusion criteria included age ≥ 18, intervention duration ≥ 4 weeks, ≥ 7 participants per group, and ≥ 1 body composition measure. Random-effects meta-analyses of the effect of breakfast skipping on body composition and cardiometabolic risk factors were performed., Results: Seven RCTs (n = 425 participants) with an average duration of 8.6 weeks were included. Compared with breakfast consumption, breakfast skipping significantly reduced body weight (weighted mean difference [WMD] = -0.54 kg [95% CI: -1.05 to -0.03], P = 0.04, I 2  = 21.4%). Percent body fat was reported in 5 studies and was not significantly different between breakfast skippers and consumers. Three studies reported on low-density lipoprotein cholesterol (LDL), which was increased in breakfast skippers as compared with breakfast consumers (WMD = 9.24 mg/dL [95% CI: 2.18 to 16.30], P = 0.01). Breakfast skipping did not lead to significant differences in blood pressure, total cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, C-reactive protein, insulin, fasting glucose, leptin, homeostatic model assessment of insulin resistance, or ghrelin., Conclusions: Breakfast skipping may have a modest impact on weight loss and may increase LDL in the short term. Further studies are needed to provide additional insight into the effects of breakfast skipping., (© 2020 The Obesity Society.)

Background and Objectives: Despite recent improvements in access to health care, many Americans still lack access to dental care. There has been a national focus on interprofessional education and team-based care to work toward the integration of services including dental care into primary care. The purpose of this systematic review is to understand the impact of implementing oral health curricula in primary care training on measurable changes in primary care practice., Methods: Researchers utilized a two-step process, first a scoping review and then using the PRISMA systematic review method to develop inclusion and exclusion criteria around audience, curricula, and outcomes to identify practice change due to oral health education curricula delivered in primary care clinician training. Researchers assessed titles, abstracts, and full texts and abstracted data for the review., Results: Researchers reviewed 2,749 articles and found 12 meeting the systematic review criteria. The reported outcomes and evaluations differed for each of the 12 studies identified. Over 40% utilized self-reporting. Seven of the included studies tracked outcomes by checklists embedded in electronic health records changes to well-child visit forms, or chart audits, one of which also tracked billing reimbursements., Conclusions: Oral health curricula for primary care clinicians are too heterogeneous to determine the effects on practice behavior. Future research should focus on developing a clear evaluation framework for measuring practice level changes in primary care settings as a result of implementing an oral health curriculum.

Objective: To describe types of recommendations represented in a curated online evidence library, report on the quality of evidence-based recommendations pertaining to diagnostic imaging exams, and assess underlying knowledge representation., Materials and Methods: The evidence library is populated with clinical decision rules, professional society guidelines, and locally developed best practice guidelines. Individual recommendations were graded based on a standard methodology and compared using chi-square test. Strength of evidence ranged from grade 1 (systematic review) through grade 5 (recommendations based on expert opinion). Finally, variations in the underlying representation of these recommendations were identified., Results: The library contains 546 individual imaging-related recommendations. Only 15% (16/106) of recommendations from clinical decision rules were grade 5 vs 83% (526/636) from professional society practice guidelines and local best practice guidelines that cited grade 5 studies (P < .0001). Minor head trauma, pulmonary embolism, and appendicitis were topic areas supported by the highest quality of evidence. Three main variations in underlying representations of recommendations were "single-decision," "branching," and "score-based.", Discussion: Most recommendations were grade 5, largely because studies to test and validate many recommendations were absent. Recommendation types vary in amount and complexity and, accordingly, the structure and syntax of statements they generate. However, they can be represented in single-decision, branching, and score-based representations., Conclusion: In a curated evidence library with graded imaging-based recommendations, evidence quality varied widely, with decision rules providing the highest-quality recommendations. The library may be helpful in highlighting evidence gaps, comparing recommendations from varied sources on similar clinical topics, and prioritizing imaging recommendations to inform clinical decision support implementation.

Aim: To investigate retrograde tracer transport by gastric enteric neurons in insulin resistant mice with low or high glycosylated hemoglobin (Hb)., Methods: Under anesthesia, the retrograde tracer fluorogold was superficially injected into the fundus or antrum using a microsyringe in KK Cg-Ay/J mice prior to onset of type 2 diabetes mellitus (T2DM; 4 wk of age), at onset of T2DM (8 wk of age), and after 8, 16, or 24 wk of untreated T2DM and in age-matched KK/HIJ mice. Six days later, mice were sacrificed by CO₂ narcosis followed by pneumothorax. Stomachs were removed and fixed. Sections from fundus, corpus and antrum were excised and mounted on a glass slide. Tracer-labeled neurons were viewed using a microscope and manually counted. Data were expressed as the number of neurons in short and long descending and ascending pathways and in local fundus and antrum pathways, and the number of neurons in all regions labeled after injection of tracer into either the fundus or the antrum., Results: By 8 wk of age, body weights of KKAy mice (n = 12, 34 ± 1 g) were heavier than KK mice (n = 17, 29 ± 1 g; F (4, 120) = 4.414, P = 0.002] and glycosylated Hb was higher [KK: (n = 7), 4.97% ± 0.04%; KKAy: (n = 6), 6.57% ± 0.47%; F (1, 26) = 24.748, P < 0.001]. The number of tracer labeled enteric neurons was similar in KK and KKAy mice of all ages in the short descending pathway [F (1, 57) = 2.374, P = 0.129], long descending pathway [F (1, 57) = 0.922, P = 0.341], local fundus pathway [F (1, 53) = 2.464, P = 0.122], local antrum pathway [F (1, 57) = 0.728, P = 0.397], and short ascending pathway [F (1, 53) = 2.940, P = 0.092]. In the long ascending pathway, fewer tracer-labeled neurons were present in KKAy as compared to KK mice [KK: (n = 34), 302 ± 17; KKAy: (n = 29), 230 ± 15; F (1, 53) = 8.136, P = 0.006]. The number of tracer-labeled neurons was decreased in all mice by 16 wk as compared to 8 wk of age in the short descending pathway [8 wk: (n = 15), 305 ± 26; 16 wk: (n = 13), 210 ± 30; F (4, 57) = 9.336, P < 0.001], local antrum pathway [8 wk: (n = 15), 349 ± 20; 16 wk: (n = 13), 220 ± 33; F (4, 57) = 8.920, P < 0.001], short ascending pathway [8 wk: (n = 14), 392 ± 15; 16 wk: (n = 14), 257 ± 33; F (4, 53) = 17.188, P < 0.001], and long ascending pathway [8 wk: (n = 14), 379 ± 39; 16 wk: (n = 14), 235 ± 26; F (4, 53) = 24.936, P < 0.001. The number of tracer-labeled neurons decreased at 24 wk of age in the local fundus pathway [8 wk: (n = 14), 33 ± 11; 24 wk: (n = 12), 3 ± 2; F (4, 53) = 5.195, P = 0.001] and 32 wk of age in the long descending pathway [8 wk: (n = 15), 16 ± 3; 32 wk: (n = 12), 3 ± 2; F (4, 57) = 2.944, P = 0.028]. The number of tracer-labeled enteric neurons was correlated to final body weight for local fundus and ascending pathways [KK: (n = 34), r = -0.746, P < 0.001; KKAy: (n = 29), r = -0.842, P < 0.001] as well as local antrum and descending pathways [KK (n = 36), r = -0.660, P < 0.001; KKAy (n = 31), r = -0.622, P < 0.001). In contrast, glycosylated Hb was not significantly correlated to number of tracer-labeled neurons [KK (n = 17), r = -0.164, P = 0.528; KKAy (n = 16), r = -0.078, P = 0.774]., Conclusion: Since uncontrolled T2DM did not uniformly impair tracer transport in gastric neurons, long ascending neurons may be more susceptible to persistent hyperglycemia and low effective insulin.

Both delayed gastrointestinal transit and autonomic neuropathy have been documented in patients with diabetes mellitus. The mechanism of neostigmine, an agent that mimics release of acetylcholine from autonomic neurons by prokinetic agents, to contract smooth muscle, despite dysfunctional enteric neural pathways, was determined using isolated ilea from STZ-treated and control guinea pigs. Both bethanechol- and neostigmine-induced contractions were stronger in diabetic ileum. Bethanechol-induced contractions of control but not diabetic ileum were increased by low dose scopolamine suggesting reduced activation of presynaptic muscarinic autoreceptors in diabetic ileum. The muscarinic receptor antagonist 4-DAMP strongly, but the nicotinic receptor antagonist hexamethonium only weakly, reduced neostigmine-induced contractions of control and diabetic ilea. The amount of acetylcholine, inferred from tissue choline content, was increased in diabetic ileum. Nicotinic neural and noncholinergic postjunctional smooth muscle receptors contributed more strongly to neostigmine-induced contractions in diabetic than control ileum. Relaxation of diabetic ileum by exogenous nitric oxide generated from sodium nitroprusside was comparable to control ileum, but smooth muscle relaxation by l-arginine using neuronal nitric oxide synthase to generate nitric oxide was weaker in diabetic ileum with evidence for a role for inducible nitric oxide synthase. Despite autonomic neuropathy, neostigmine strongly contracted ileum from diabetic animals but by a different mechanism including stronger activation of postjunctional muscarinic receptors, greater synaptic acetylcholine, stronger activation of noncholinergic excitatory pathways, and weaker activation of inhibitory pathways. A selective medication targeting a specific neural pathway may more effectively treat disordered gastrointestinal transit in patients with diabetes mellitus., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Delayed gastric emptying and autonomic neuropathy have been documented in patients with diabetes mellitus. Some medications used to treat delayed gastric emptying enhance release of acetylcholine from autonomic neurons to strengthen gastric contractions. Autonomic coordination among gastric regions may be altered in diabetes resulting in poor outcomes in response to prokinetic drugs. Fundus, antrum, and pylorus from STZ or control guinea pigs were treated with neostigmine to mimic release of acetylcholine from autonomic neurons by prokinetic agents. In diabetic animals, neostigmine-induced contractions were weaker in fundus and pylorus but similar in antrum. The muscarinic receptor antagonist 4-DAMP or the nicotinic receptor antagonist hexamethonium reduced neostigmine-induced contractions. Activation of presynaptic muscarinic receptors on nitrergic neurons was impaired in fundus and antrum from diabetic animals. Nerve-stimulated contractions and relaxations, number of nNOS myenteric neurons, and tissue choline content were reduced in fundus from diabetic animals. Despite reduced number of myenteric neurons, tissue choline content was increased in antrum from diabetic animals. Since cholinergic motility of each gastric region was affected differently by diabetes, prokinetic drugs that nondiscriminately enhance acetylcholine release from autonomic neurons may not effectively normalize delayed gastric emptying in patients with diabetes and more selective medications may be warranted., (Copyright © 2010 Elsevier B.V. All rights reserved.)